DDT is not only effective against malaria vectors but is equally potent at alleviating various other arthropod-borne diseases such as yellow fever, African sleeping sickness, dengue fever and typhus. However, DDT was also extensively used in agriculture where enormous quantities were aerially sprayed onto crops to curb pests.
This widespread and uncontrolled use of DDT raised concerns in the s amongst environmentalists who described possible catastrophic consequences for both the environment and humans leading to the ban of DDT use in the s Weissmann, Little scientific evidence, however, exists to support these concerns and no toxic effects caused by DDT in humans have been noted when used in low concentrations as required for the control of malaria vectors inside houses Rogan and Chen, Since then, the efforts of several public health officials and malaria experts have resulted in the restricted use of DDT in Africa for malaria vector control only and not in agriculture Dugger, Malaria parasite transmission can additionally be prevented by the treatment of parasite vectors with a drug that blocks the sexual development of the parasites within the mosquito.
Coleman tested the effect of 8-aminoquinolines on the sexual development of P. The drug-fed mosquitoes produced fewer oocysts than the control-fed group, and in addition, the sporozoites that did manage to develop from the oocysts could not enter the salivary glands of the mosquito, and therefore prevented the parasites from being transmitted back to the mice Coleman et al. The antifolate drugs proguanil and pyrimethamine have also been shown to be sporontocidal. These drugs caused a reduction in oocysts in sensitive strains and pyrimethamine was also reported to directly damage ookinetes Bray et al.
Only one mouse out of 16 exposed to DFMO-treated mosquitoes contracted malaria. DFMO thus exerts its most deleterious effects on the stages where active cell division is taking place, namely the exo-erythrocytic schizogonous and sporogonous stages Gillet et al.
The development of a safe and effective vaccine against infection represents an alternative method for treating parasitic diseases. Despite extensive efforts, not a single vaccine against any of the human parasitic diseases is currently available. Some malaria experts, however, remain adamant that vaccination may be the most valuable strategy for reducing mortality associated with malaria Miller and Hoffman, People living in malaria endemic areas develop low levels of protective immunity against P.
Protective immunity is therefore lost once the host moves into an area where a different strain resides and also once the host is no longer chronically infected Bull and Marsh, Current vaccine development strategies focus on different protein antigens that are expressed during the different stages of the life cycle, namely the pre-erythrocytic sporozoite and schizont-infected hepatic cells , the asexual intra-erythrocytic merozoiteinfected erythrocytes and sexual exo-erythrocytic gametocyte stages Figure 1.
An ideal vaccine against malarial infection should therefore induce immune responses against every stage of the life cycle. Such a multistage, multivalent and multi immune response vaccine presents the best strategy for a successful vaccine in the treatment of malaria Doolan and Hoffman, Antibodies directed against antigens on the surface of extracellular sporozoites e.
The areas where malaria is prevalent at epidemic proportions are mostly devoid of trained physicians and health workers who possess the skills necessary for the early diagnosis of the disease as well as its efficient treatment. Novel antimalarials must be orally bioavailable, as the diseased individuals will most probably not have access to facilities such as hospitals and clinics.
The treatment time period must also be less than a week to reduce the risks associated with the development of parasite resistance to the drugs, which may also be reduced with the use of combination-based therapy. Finally, the drugs must be cheap and have a relatively extended shelf life Nwaka and Hudson, As with the vaccines, anti-malarials target different stages of the parasite life cycle within the human host and specifically interfere with processes that are essential to parasite survival.
Eradication of malaria with the use of anti-malarials is, however, continuously compromised by the increased prevalence of parasite resistance to the small amount of available commercial drugs.
A schematic diagram of the parasite life cycle within the human host showing the targets of different anti-malarials during the developmental stages. The pre-erythrocytic, asexual intra-erythrocytic and sexual exo-erythrocytic stages are shown. The different intra-erythrocytic phases of malaria parasite development are also given. Finally, drugs that have been used at each stage are shown in the dashed boxes Chauhan and Srivastava, ; Olliaro, ; Korenromp et al.
Different antimalarial drug classes together with their mechanisms of action Compiled from Chauhan and Srivastava, ; Olliaro, ; Korenromp et al. Hydroxynaphthoquinone Atovaquone also sporontocidal Interferes with cytochrome electron transport. Pyrimidines Pyrimethamine also sporontocidal and interferes with sexual reproduction Inhibits DHFR used in combination with sulfadoxine or dapsone 4-Methanolquinoline Mefloquine Inhibits haem detoxification.
Sesquiterpene lactone Artemisinin and derivatives also gametocytocidal Inhibits calcium adenosine triphosphatase. Exo- Antibiotics Tetracycline also active against intra- erythrocytic forms Inhibitors of aminoacyl-tRNA binding during protein synthesis. Doxycycline also active against intra- erythrocytic forms Inhibitors of aminoacyl-tRNA binding during protein synthesis. The bark of the Cinchona tree has been used for centuries to treat fever associated with malarial infection from which the active ingredient is quinine.
It remained the anti-malarial of choice until the s, when other anti-malarials such as its chloroquine derivative replaced quinine. Quinine, however, is still used today to treat clinical malaria and not as a prophylaxis due to its side effects and poor tolerability. Chloroquine is a 4-aminoquinoline derivative of quinine and for many years it was the main anti-malarial drug used in the treatment of malaria until parasite resistance developed in the s.
It remains the most popular anti-malarial developed to date due to its safety, low cost and efficacy. Bjorkman and Phillips-Howard, ; Yeh and Altman, Today, the widespread resistance to the drug has rendered its use as a therapeutic agent useless, even though it still shows some efficacy in the treatment of the other human malaria parasites Korenromp et al. Despite more than three decades of research, the exact molecular mechanism of chloroquine action remains a controversial topic.
It is believed that the weak-base drug accumulates in the acidic food vacuole of the parasite where it prevents haem detoxification Bray et al. Both these proteins are localised to the food vacuole membrane.
Mutations in these genes could lead to small increases in the food vacuole pH thus reducing the amount of chloroquine that can accumulate, rendering the drug ineffective Spiller et al. Alternatively, PfCRT may increase the efflux of chloroquine by directly interacting with the drug Cooper et al.
Resistance is associated with several mutations in the PfCRT protein, while the loss of a Lys residue at position 76 has been shown as the critical mutation rendering the P. This residue is located within the first transmembrane segment of PfCRT and may therefore play an important role in the properties of the channel or transporter Cooper et al. Mutations in the Pfmdr1 gene is associated with resistance to mefloquine, quinine and halofantrine Reed et al. A number of related aminoquinolines have since been developed and applied, including:.
The antifolates are some of the most widely used anti malarials. However, their role in malaria prevention is hampered by the rapid emergence of resistance once the parasites are placed under drug pressure. The direct effect of folate biosynthesis inhibition is a reduction in the synthesis of the amino acids serine and methionine as well as in pyrimidines, which leads to decreased synthesis of DNA. The antifolate drugs target the intra-erythrocytic stages as well as the gametocytes of P.
The antifolates can generally be divided into two classes; the type-1 antifolates mimic the p- aminobenzoic acid pABA substrate of dihydropteroate synthase DHPS and include the sulfonamides sulfadoxine and sulfones dapsone , while the type-2 antifolates pyrimethamine and proguanil inhibit dihydrofolate reductase DHFR Olliaro, In addition, malaria parasites are capable of in vivo folate salvage from the extracellular environment as well as synthesising folate derivatives from simple precursors.
The mechanism of exogenous folate uptake by a carrier-mediated process has important implications in increasing the sensitivity of the antifolate inhibitors and is being investigated as a novel drug target Wang et al. Pyrimethamine crosses the blood-brain barrier as well as the placenta. Resistance to sulfadoxine-pyrimethamine combination therapy, however, emerged rapidly due to the appearance of point mutations in the active sites of the target enzymes resulting in reduced drug binding capacity Cowman and Lew, ; Plowe et al.
Artemisinin is a sesquiterpene lactone extracted from the leaves of Artemisia annua. It is a potent, fast acting blood schizontocide that shows efficacy against all Plasmodium species. Its efficacy is especially broad and shows activity against all the asexual stages of the parasites including the gametocytes Figure 1.
The latter makes this class of antimalarials especially important as they reduce the transmission potential through its gametocytocidal activity. Originally the mechanism of action of artemisinin was thought to be mediated by the peroxide ring of the drug, which is cleaved and activated by ferrous iron in the heme stores into toxic free radicals that can subsequently damage intracellular targets via alkylation Meshnick et al.
Recently, however, this theory was challenged by evidence that artemisinin exerts its inhibitory effects on the malarial sarcoplasmic-endoplasmic reticulum calcium ATPase SERCA resulting in an alteration of intracellular calcium levels Eckstein-Ludwig et al. The exact mechanism of action, however, remains elusive and different studies have produced contradicting results [reviewed in Krishna et al.
Several derivatives of artemisinin have been developed since artemisinin itself is poorly absorbed and include dihydroartemisinin, artesunate sodium salt of the hemisuccinate ester of artemisinin , artemether methyl ether of dihydroartemisinin and artemether ethyl ether of artemisinin Korenromp et al.
Currently, the WHO recommends artemisinin-based combination therapy ACT as the first-line treatment against malaria infections where resistance to other antimalarials is prevalent.
One of the obvious disadvantages of using ACT for malaria case-management in Africa is the increased cost involved in combining therapies. Even so, several reasons exist for combining antimalarials with an artemisinin derivative, namely: Several ACTs that have been developed are listed below. Evidence for in vitro resistance to an artemisinin derivative, however, appeared in field isolates from French Guiana in The increased artemether IC50s were ascribed to the presence of a mutation in the SERCA PfATPase6 gene and was attributed to inappropriate drug use that exerted selection pressures, favouring the emergence of parasites with an artemether-resistant in vitro profile.
Even though reduced in vitro drug susceptibility is not tantamount to diminished therapeutic effectiveness, it could lead to complete resistance and thus called for the rapid deployment of drug combinations Jambou et al. No resistance has been detected to date Bathurst and Hentschel, Several antibiotics such as tetracycline, doxycycline and minocycline are active against the exo-erythrocytic as well as the asexual blood stages of the P. The tetracyclins are antibiotics that were originally derived from Streptomyces species, but are usually synthetically prepared.
This is due to the presence of genomes in the mitochondrion and apicoplast that encode prokaryote-like ribosomal RNAs, tRNAs and various proteins Wilson et al.
Doxycycline is a synthetic tetracycline derivative with a longer half-life than tetracycline. A disadvantage of these type of antibiotics as antimalarials is the development of photosensitivity during treatment, which is an obvious drawback for tourists entering malaria areas Korenromp et al.
It is a small herb that grows up to 60 cm in height. The plant is quite herbaceous unlike P. Its leaves are small and appear oblong with very short or absent petiole. The flowers are numerous, white to greenish in colour and minute, grouping at the axillary with a pedicel. The fruit is a smooth surface and glabose capsule, Wiart, It belongs to the Euphorbiaceae family with a worldwide distribution. Some people who do not have immunity against malaria. They must provide the dieses to make sure full recovery.
People who are suspected malaria must Isolated and diagnosed and treated immediately to prevent the spread of the disease especially among children. Essay UK - http: If this essay isn't quite what you're looking for, why not order your own custom Medicine essay, dissertation or piece of coursework that answers your exact question? There are UK writers just like me on hand, waiting to help you.
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- Malaria Introduction to Malaria Malaria is a deadly disease, responsible for ,, malaria-infected people and over a million deaths annually. It is caused by malaria parasites that have infected mosquitoes, so the disease is transferred into a person’s blood when the mosquito bites us.
Roll Back Malaria Essay Words | 10 Pages. Malaria is an important public health disease endemic in over a hundred countries globally. About 90% of malaria deaths occur in Africa with a child dying every forty five seconds.
Malaria is caused by species of parasites of the genus Plasmodium that affect humans (P. falciparum, P. vivax, P. ovale, and P. malariae). The Anopheles vector is the link between man and the malaria . Most malaria cases seem to cluster in the tropical climate areas extending into the subtropics, and malaria is especially endemic in Africa. In eighty percent of all reported cases were in Africa, while the remainder of most cases came from nine countries: India, Brazil, Afghanistan, Sri-Lanka, Thailand, Indonesia, Vietnam, Cambodia, and China.
Essay on Malaria Malaria is a life-threatening disease caused by parasites that are transmitted to humans by bites of infected mosquitoes. In , malaria has led to nearly deaths, mostly among African children (The World Health Organization, ). Generally, malaria is an infectious disease caused by Plasmodium which is a parasite that infects red blood cells. There are five types of malaria which are Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium falciparum and Plasmodium knowlesi. Malaria is usually transmitted from human-to-human by the Anopheles mosquito.